Varicoceles are an abnormal dilation of the pampiniform plexus of veins within the scrotum. Varicoceles are highly prevalent and can result in a myriad of deleterious effects on male reproduction. Numerous therapeutic options are available for correcting varicoceles, including surgical varicocelectomy and radiographic venous embolization. Varicocele correction is a more cost-effective therapeutic modality than both intrauterine insemination (IUI) and in vitro fertilization (IVF) for affected couples. In summary, varicoceles contribute significantly to male reproductive pathology, and varicocele correction is an important option for both clinicians and patients to consider in this era of assisted reproductive techniques.
Key points
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Varicoceles are present in 35% to 40% of infertile men and represent a highly treatable form of male infertility.
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Varicoceles can result in disordered spermatogenesis, germ cell sloughing within the seminiferous tubules, testicular atrophy, and decreased testosterone secretion.
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Microsurgical varicocelectomy results in improved semen parameters and reproductive outcomes with low rates of recurrence and postoperative morbidity.
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Varicocelectomy is more cost-effective than both IUI and in vitro fertilization as a treatment option for affected infertile couples.
Historical perspective
The association of the varicocele with male infertility derives back to the first century AD when Celsius reported a link between dilated scrotal veins and testicular atrophy. Besides supportive clothing, no known intervention was offered for symptomatic painful varicoceles until the nineteenth century when various methods were established to ligate these dilated veins. Among them was the Woods operation, which consisted of the passing of wire loops around the scrotal vessels and applying tension until they eventually cut themselves out. Another popular modality involved the use of Andrew varicocele clamp, which removed the dilated vessels along with the scrotal skin covering these vessels. Several modifications were made on these “varicocelectomy” techniques, but the main indication for surgery was scrotal discomfort secondary to varicocele.
The benefits of varicocelectomy with regards to male reproduction were not recognized until the late nineteenth century. In 1885, Barwell reported on 100 men with varicoceles who underwent placement of wire loops around dilated scrotal veins and observed an improvement in testicular size and consistency. Testicular function was augmented by Bennet in 1889, when he reported an improvement in semen quality in a patient who underwent bilateral varicocelectomy. In 1929, Macomber and Sanders further elucidated the reproductive benefit to varicocelectomy by reporting normal semen parameters and fertility after the procedure in an oligozoospermic subfertile patient. Despite these early reports, varicocelectomy did not gain popularity as a surgical treatment of male infertility until the work of Tulloch in 1955. In his series of 30 patients undergoing unilateral or bilateral varicocelectomy, he demonstrated an improvement in semen parameters in 26 patients, of which 10 had return to normal fertility with successful pregnancy. His conclusion that “where a varicocele is associated with subfertility, the varicocele should be cured” has become part of the backbone of reproductive medicine, and numerous studies have followed demonstrating an improvement in semen parameters and pregnancy rates in infertile men undergoing this procedure. These more contemporary series on varicoceles and treatment options, including outcomes data, are reviewed in further sections.
The varicocele clamps and wire loops were discontinued in the early twentieth century as the ligation or excision of the pampiniform plexus transformed to varicocelectomy through the inguinal or scrotal route. Because of the high failure rate and the risk of injury to end arteries through the scrotal approach, Ivanissevich advocated “high ligation of the internal spermatic vein” through either the high inguinal or retroperitoneal approach. In 1960, he further documented his experience with 4470 operative cases, demonstrating both low complication and failure rates, and many surgeons continue to use some modification of this technique today. More advances in varicocelectomy came through the use of microsurgery in the 1980s, when several published series demonstrated not only greater efficacy but also a reduction in morbidity through better preservation of the internal spermatic artery and lymphatic channels with higher magnification.
Historical perspective
The association of the varicocele with male infertility derives back to the first century AD when Celsius reported a link between dilated scrotal veins and testicular atrophy. Besides supportive clothing, no known intervention was offered for symptomatic painful varicoceles until the nineteenth century when various methods were established to ligate these dilated veins. Among them was the Woods operation, which consisted of the passing of wire loops around the scrotal vessels and applying tension until they eventually cut themselves out. Another popular modality involved the use of Andrew varicocele clamp, which removed the dilated vessels along with the scrotal skin covering these vessels. Several modifications were made on these “varicocelectomy” techniques, but the main indication for surgery was scrotal discomfort secondary to varicocele.
The benefits of varicocelectomy with regards to male reproduction were not recognized until the late nineteenth century. In 1885, Barwell reported on 100 men with varicoceles who underwent placement of wire loops around dilated scrotal veins and observed an improvement in testicular size and consistency. Testicular function was augmented by Bennet in 1889, when he reported an improvement in semen quality in a patient who underwent bilateral varicocelectomy. In 1929, Macomber and Sanders further elucidated the reproductive benefit to varicocelectomy by reporting normal semen parameters and fertility after the procedure in an oligozoospermic subfertile patient. Despite these early reports, varicocelectomy did not gain popularity as a surgical treatment of male infertility until the work of Tulloch in 1955. In his series of 30 patients undergoing unilateral or bilateral varicocelectomy, he demonstrated an improvement in semen parameters in 26 patients, of which 10 had return to normal fertility with successful pregnancy. His conclusion that “where a varicocele is associated with subfertility, the varicocele should be cured” has become part of the backbone of reproductive medicine, and numerous studies have followed demonstrating an improvement in semen parameters and pregnancy rates in infertile men undergoing this procedure. These more contemporary series on varicoceles and treatment options, including outcomes data, are reviewed in further sections.
The varicocele clamps and wire loops were discontinued in the early twentieth century as the ligation or excision of the pampiniform plexus transformed to varicocelectomy through the inguinal or scrotal route. Because of the high failure rate and the risk of injury to end arteries through the scrotal approach, Ivanissevich advocated “high ligation of the internal spermatic vein” through either the high inguinal or retroperitoneal approach. In 1960, he further documented his experience with 4470 operative cases, demonstrating both low complication and failure rates, and many surgeons continue to use some modification of this technique today. More advances in varicocelectomy came through the use of microsurgery in the 1980s, when several published series demonstrated not only greater efficacy but also a reduction in morbidity through better preservation of the internal spermatic artery and lymphatic channels with higher magnification.
Anatomy
A varicocele is defined as a dilatation or tortuosity of the veins of the pampiniform plexus. Clinically, they are found more commonly on the left side, although there is wide variation among the reported prevalence of bilateral varicoceles, which range from 30% to 80%. An isolated right-sided varicocele is extremely rare and raises concern about an underlying retroperitoneal mass.
The reason for the prevalence of left varicoceles can be clarified by retroperitoneal anatomy. The left internal spermatic vein drains perpendicularly into the left renal vein, whereas the right internal spermatic vein drains obliquely into the vena cava. This basic finding has 2 ramifications that contribute to the left-sided predisposition. For one, the course of the left internal spermatic vein results in a length of approximately 8 to 10 cm longer than its right-sided counterpart. This added length, coupled with upright posture, results in increased hydrostatic pressure, which can overcome valvular mechanisms in certain men and lead to dilatation and tortuosity of spermatic veins. Second, the perpendicular insertion of the left internal spermatic vein into the left renal vein exposes the left spermatic vein to pressure elevations within the left renal vein. The oblique insertion of the right internal spermatic vein into the vena cava, on the contrary, shields the right internal spermatic vein from the increased pressures within the vena cava. The basis for increased hydrostatic pressure and varicocele formation is best elucidated by the work of Shafik and Bedeir, who studied venous tension patterns in spermatic cord veins in 32 patients with a left varicocele and 30 controls. They demonstrated that patients with left varicoceles have a venous tension that is considerably higher both during rest and during Valsalva maneuver compared with that in control subjects, with average increases of 19.7 mm Hg and 22 mm Hg, respectively.
The predisposition to varicocele formation is also related to abnormalities in valvular mechanisms among certain patients. In a well-quoted study, Ahlberg and colleagues performed anatomic examination of 30 normal men at autopsy and revealed the complete absence of valves in 40% of the left spermatic veins and 23% of the right spermatic veins. In a follow-up study, Ahlberg and colleagues performed selective phlebography in patients with varicoceles and control subjects in the erect position; they demonstrated retrograde left internal spermatic vein filling in 22 patients with varicoceles and right internal spermatic vein filling in 10 patients. They reported that some of these patients had no valves and others had incompetent valvular mechanics. Meanwhile, they did not observe any retrograde filling in 9 control patients and 6 patients who underwent previous varicocelectomy. These studies articulate 2 important points: first, valvular malfunction or absence does exist in a certain segment of the population, and second, the absence of valves is more common in the left internal spermatic vein.
There may also be a genetic basis to the valvular dysfunction leading to varicocele development. Raman and colleagues evaluated 62 first-degree relatives of patients with varicoceles and found that 56.5% of them had a clinically palpable varicocele on physical examination, compared with a prevalence of 6.8% in 263 controls. Specifically, among the first-degree relatives with varicoceles, 74% were brothers, 41% were fathers, and 67% were sons. Although the genetic mechanisms predisposing to varicocele formation remain to be elucidated, these results suggest an inheritance pattern of this anatomic finding.
Most anatomic research has been conducted on the internal spermatic vein and varicocele formation; however, there are some data to suggest that dilated external spermatic (cremasteric) veins can also contribute to primary or recurrent varicoceles. In 1980, Coolsaet retrospectively reviewed 67 patients with left varicoceles who underwent preoperative venography and demonstrated that the cause of varicoceles stems from dysfunction within the internal spermatic vein, obstruction of the common iliac vein (resulting in dilated external spermatic veins), or both mechanisms. Murray and colleagues evaluated 44 varicocele recurrences and reported that 58% of these are due to inguinal (external spermatic) collaterals. Using 4 mm as the threshold for vein dilation, Chehval and Purcell identified dilated external spermatic veins in 49.5% of 93 varicoceles in 67 patients. It is generally acknowledged that these external spermatic veins can lead to varicocele formation and recurrence, and standard inguinal or subinguinal varicocelectomy calls for routine inspection and ligation of these external spermatic collaterals. In addition to demonstrating varicocele recurrences due to venous collaterals that bypass the inguinal portion of the spermatic cord, Kaufman and colleagues report that 7% of recurrences are due to scrotal collaterals. This finding forms the basis for delivery of the testicle during varicocelectomy and ligation of all gubernacular veins exiting from the tunica vaginalis. Goldstein and colleagues report a lower recurrence rate (0.6%) with delivery of the testis and adaption of the microsurgical technique.
Pathophysiology
It is well acknowledged that varicoceles can cause progressive testicular damage and infertility. Lipshultz and Corriere demonstrated that varicoceles result in testicular atrophy in both fertile and subfertile men. Multiple histologic studies have explored this phenomenon on the microscopic level. Not only is there the loss of testicular mass with varicoceles, but also there can be substantial areas of testicular dysfunction. Scott reported his findings after having performed bilateral testicular biopsies in 17 patients with unilateral varicoceles; he found hypospermatogenesis with decreased thickness of germinal epithelium in both testes. Several others have confirmed his findings and have also reported areas of spermatogenic arrest, sloughing of spermatogenic cells, and “Sertoli cell only” histology associated with the presence of unilateral varicoceles. Saleh and colleagues reported testicular biopsy results from 37 azoospermic men with varicoceles; these revealed complete spermatogenesis with disorganization, sloughing, and low to moderate sperm counts in 30%, arrested spermatogenesis in 38%, and “Sertoli cell only” histology in 32% of cases. Despite the extensive testicular dysfunction in these azoospermic men, the authors showed that the degree of histopathologic impairment is independent of the clinical grade of the varicocele. The same degree of testicular damage was equally associated with either grade I or grade III varicoceles.
It remains unclear when an otherwise incidental varicocele may become pathologic. Gorelick and Goldstein reported that varicoceles were palpable in 35% of men presenting with primary infertility and in 81% of men with secondary infertility. The men with secondary infertility had significantly lower mean sperm concentration, poorer morphology, and higher follicle-stimulating hormone levels than did men with varicoceles and primary infertility. Their findings suggest that varicoceles cause a progressive decline in fertility and can continue to induce impairment of spermatogenesis, despite prior fertility. Chehval and Purcell followed men with varicoceles presenting for fertility evaluation at 9- to 96-month intervals and found a statistically significant deterioration in sperm density and motility, suggesting progressive testicular deterioration.
There are several hypotheses that attempt to explain the correlation between varicoceles and testicular dysfunction. The most widely acknowledged mechanism is that of testicular hyperthermia. Human testicles are approximately 1°C to 2°C less than normal body temperature. Scrotal thermoregulation is maintained by thin scrotal skin, which lacks subcutaneous fat and a countercurrent heat exchange system involving the pampiniform plexus. This system, first proposed by Dahl and Herrick, allows arterial blood to be cooled as it is delivered to the testis and enables the lower temperatures ideal for testicular function. In most men, scrotal temperatures are lowest during the standing position; however, standing also intensifies varicoceles and may prevent the reduction in testicular temperature. In 1973, Zorgniotti and Macleod reported that oligozoospermic patients with varicoceles had bilateral intrascrotal temperatures that were significantly higher by 0.6°C to 0.7°C than those of normal controls. Goldstein and Eid used sensitive needle thermistors to measure intratesticular and bilateral scrotal surface temperatures in anesthetized infertile men with unilateral varicoceles and normal controls, and they demonstrated an average temperature increase of 2.5°C in men with varicoceles. Several other studies have demonstrated an increase in intrascrotal temperature in men with varicoceles, although there is controversy on the amount of elevation.
Animal and human studies show that this additional heat can be detrimental to spermatogenesis. Lue and colleagues exposed the scrota of rats to 43°C for 15 minutes, which resulted in increased apoptosis for spermatocytes and spermatids. Yin and colleagues, using an adult mouse model of experimental unilateral cryptorchidism, showed that exposure of the testis to abdominal temperature results in increased DNA fragmentation, loss of testicular weight, histologic evidence of germ cell loss, and widespread apoptosis of germ cells (particularly primary spermatocytes and round spermatids). Although human studies also confirm the association between varicoceles, elevated scrotal temperatures, and testicular dysfunction, not all men with varicoceles share this phenomenon. Lewis and Harrison demonstrated that men with varicoceles and abnormal spermatogenesis had higher scrotal temperatures compared with men with varicoceles and normal results in semen analyses. To confound the picture further, Mieusset and colleagues demonstrated that infertile men with abnormal spermatogenesis have higher scrotal temperatures compared with fertile men, regardless of the presence of a varicocele. Although the scrotal temperatures of infertile men with varicoceles were significantly higher than those of fertile men, they did not differ significantly from those of infertile men without varicoceles.
The persistence of scrotal hyperthermia and abnormal semen parameters in only some men with varicoceles remains a clinical mystery. Numerous studies have investigated various molecular markers in men with varicoceles to see why these dilated tortuous veins have a harmful effect on spermatogenesis in only some men. One interesting theory involves the heat shock proteins (HSPs) and heat shock factors (HSFs), both of which generally have a protective function. Activated by increased temperature and stress, HSPs and HSFs serve as molecular chaperones that mitigate the stress-induced denaturation of other proteins, allowing cells to survive in potentially lethal conditions. Lima and colleagues have shown that the gene expression of one particular HSP, HSPA2, is downregulated in adolescents with varicoceles and oligozoospermia compared with both adolescents without varicoceles and adolescents with varicoceles and normal sperm concentration. Yeşilli and colleagues confirmed that HSPA2 level is lower in patients with varicoceles and abnormal semen parameters and that this expression increases significantly after varicocelectomy. These studies suggest that HSPA2 expression may be a marker of thermal tolerance in men with varicoceles. Other studies have demonstrated additional HSPs and HSFs in ejaculated sperm of men with varicoceles and impaired spermatogenesis, although the clinical significance of these molecular markers requires further investigation.
Hypoxia and oxidative stress also play a role in varicocele pathophysiology. In a rat varicocele model, Kilinç and colleagues demonstrated that the levels of various markers for hypoxia and angiogenesis, namely, hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor, were significantly elevated in rats with surgically induced varicoceles compared with a sham operated cohort and a control group. In men with a grade 3 unilateral varicocele undergoing varicocelectomy, Lee and colleagues demonstrated that HIF-1alpha expression is 7-fold higher in the internal spermatic vein compared with control subjects. Both these studies confirm that varicoceles are associated with increased hypoxia, and this may contribute to testicular dysfunction. Further, increased oxidative stress has also been associated with varicoceles. Hendin and colleagues demonstrated that patients with varicoceles had significantly higher reactive oxygen species (ROS) levels compared with controls; however, these levels did not differ significantly between infertile men with varicoceles and fertile men with varicoceles. Likewise, total antioxidant levels were significantly lower among men with varicoceles, regardless of fertility status. Other markers for oxidative stress, namely, nitrotyrosine and 4-hydroxy-2-nonenal–modified proteins, have also been identified in men with varicoceles. ROS production in semen has been associated with loss of sperm motility, decreased capacity for sperm-oocyte fusion, and loss of fertility. Surgical correction of the varicocele is associated with decreased oxidative stress; Mostafa and colleagues reported that varicocelectomy results in a significant reduction in ROS levels and also an increase in the antioxidant capacity of semen in infertile men.
The reflux of renal and adrenal metabolites into the spermatic vein is also hypothesized to contribute to varicocele pathophysiology. Given venography studies, which demonstrate reflux of blood from the renal vein to the spermatic vein, along with venous pooling secondary to the dilation and tortuosity of the varicocele, it is thought that these renal and adrenal metabolites can be toxic to testicular function. However, there is considerable inconsistency among studies examining the presence of these metabolites in reproductive tissues. Comhaire and Vermeulen reported increased catecholamine levels in the internal spermatic vein of patients with varicoceles, but other investigators were unable to confirm this finding. Elevated levels of prostaglandins E and F, both of which are antispermatogenic in animal models, have been identified in the internal spermatic vein in patients with varicoceles. In addition, elevated levels of the potent vasodilator adrenomedullin have been identified in the spermatic vein of patients presenting for varicocele repair; it is thought that this metabolite may disturb the countercurrent heat exchange system of the spermatic cord.
Hormonal dysfunction has also been associated with varicoceles and can contribute to their pathophysiology. Animal studies using surgically induced varicoceles show subsequent reductions in serum and intratesticular testosterone levels. Comhaire and Vermeulen have demonstrated that decreased plasma testosterone concentrations are found in men with varicoceles. In one of the largest studies to date, the World Health Organization published data on 9034 men presenting for an infertility evaluation and reported that men older than 30 years with varicoceles had significantly lower testosterone levels than younger men with varicoceles. Meanwhile, this trend was not observed in men without varicoceles, suggesting a progressive detrimental effect of the varicocele on Leydig cell function. However, other reputable series have not shown any significant differences in plasma testosterone in men with varicoceles compared with normal men. Additional studies suggest Leydig cell dysfunction and decreased testosterone synthesis in some men with varicoceles. Weiss and colleagues reported that the testicular tissue of men with varicoceles and severe oligozoospermia have suppression of in vitro testosterone synthesis compared with normal controls. Sirvent and colleagues studied testicular histology in men with varicoceles and reported increased Leydig cell cytoplasmic vacuolization and atrophy and a decrease in the total number of Leydig cells; this was true of bilateral testicular tissue in men with a unilateral varicocele.
The reversibility of Leydig cell dysfunction with varicocele treatment remains controversial. With retroperitoneal varicocelectomy, historical studies by Hudson and colleagues and Segenriech and colleagues report an insignificant increase in testosterone from preoperative levels, although both study populations were small (14 and 24 patients, respectively). Conversely, Su and colleagues reported a statistically significant increase in serum testosterone levels in 53 infertile men with varicoceles undergoing microsurgical inguinal varicocelectomy. Mean serum testosterone increased from a preoperative level of 319 to 409 ng/dL, suggesting that varicocelectomy can improve Leydig cell function in men with varicoceles. In addition, they found an inverse correlation between preoperative testosterone levels and change in testosterone levels after varicocelectomy, which suggests that patients with lower preoperative serum testosterone levels and potentially more testicular dysfunction might achieve the greatest benefit from varicocele treatment. Tanrikut and colleagues reported data on 200 men undergoing varicocelectomy and reported a significant increase in serum testosterone levels in 70% of patients; however, they did not find any association between change in testosterone level and age, laterality of varicocele, or varicocele grade. These findings confirm the benefit to varicocelectomy in improving testicular function in some men and also suggest that the improvement in testosterone biosynthesis is independent of age and varicocele severity. Nonetheless, the reversibility of hormonal dysfunction by varicocelectomy remains controversial, and, to date, no best practice policy statements or guidelines advocate varicocelectomy for isolated hypogonadism.
Presentation
Varicoceles are present in 15% to 20% of the general population but in approximately 35% to 40% of men presenting for an infertility evaluation. Any man presenting with a known varicocele who has a possible interest in future paternity should be offered a thorough medical and reproductive history, a physical examination, a hormone profile, and semen analysis testing.
Diagnosis
A meticulous physical examination is paramount to accurately diagnosing a varicocele. Ideal conditions include a warm room, a comfortable and cooperative patient, and a skilled clinician. To facilitate examination of the scrotal contents, the scrotum should be warm and relaxed. A cold environment or uncomfortable patient may result in shrinkage or tightening of the scrotum, which can make a varicocele more difficult to palpate. Some clinicians have even recommended a heating pad to ensure the accuracy of the physical examination. The patient should be examined in both the recumbent and upright positions.
These tortuous dilated veins have been described as a “bag of worms” by Dubin and Amelar and may be significantly reduced or even disappear when the patient is in the supine position. When a varicocele is suspected but not clearly palpable, the patient should perform a Valsalva maneuver in the standing position. This exercise will enable the dilated veins to become more engorged, and the clinician may palpate a discrete pulse when examining the cord. Typical findings include dilated veins above the testis within the spermatic cord, most commonly on the left side, along with ipsilateral or bilateral testicular atrophy. Although isolated right varicoceles do occur, they are extremely rare and should raise the question of an underlying retroperitoneal process such as lymphadenopathy. Furthermore, varicoceles that do not reduce in the supine position should raise the same concern and merit further investigation.
The varicocele grading system, as proposed by Dubin and Amelar, as is follows:
| Grade 1, small | Palpable only with the patient standing and performing a concurrent Valsalva maneuver |
| Grade 2, moderate | Palpable with the patient standing, without a Valsalva maneuver |
| Grade 3, large | Visible through the scrotal skin and palpable with the patient standing |
Clinical varicoceles are defined as varicoceles that are palpable on physical examination, and only these varicoceles have been associated with infertility. Although there are several radiologic modalities available, routine use of imaging studies is not recommended for the detection of subclinical varicoceles in patients without a palpable abnormality.
Ultrasonography
Scrotal ultrasonography is not indicated for routine evaluation of men with varicoceles. However, in a situation in which the physical examination is inconclusive, scrotal ultrasound examination can be used for clarification. Chiou and colleagues demonstrated a sensitivity of 93% and specificity of 85% for color flow Doppler ultrasonography (CDU) when compared with physical examination ( Fig. 1 ). All moderate to large varicoceles found on physical examination were detected by CDU diagnosis. Petros and colleagues demonstrated that CDU detected 93% of varicoceles found on physical examination and provided the best correlation with venography. Thus, in situations in which physical examination may be challenging due to scrotal size or skin thickness, CDU may be a useful adjunct to the diagnosis of varicocele.
Caution with scrotal ultrasonography persists because of the detection of subclinical varicoceles and the controversy surrounding their management. Mihmanli and colleagues used CDU in 208 testes units in infertile patients without clinical varicoceles on physical examination and detected 94 subclinical varicoceles. However, correction of subclinical varicoceles has not been proved to positively affect fertility. Grasso and colleagues randomized 68 infertile patients with subclinical varicoceles to varicocelectomy versus observation and found no improvement in sperm quality or paternity. Yamamoto and colleagues reported similar findings in 85 infertile patients; they noted an improvement in sperm density, but there were no significant differences in sperm motility, morphology, or pregnancy rate. Because of the dearth of data showing any reproducible benefit for the treatment of subclinical varicoceles, widespread use of ultrasonography to screen for dilated spermatic veins is not advocated.
Scrotal ultrasonography is useful in patients who have undergone prior surgery and in whom recurrence or persistence of varicocele is suspected. In addition, ultrasonography is more accurate than physical examination or orchidometer when assessing testicular size, especially when there is the concern for progressive testicular atrophy. Thus, although ultrasonography is not routinely used in the diagnosis of varicocele, it may supplement physical examination findings in some cases and should be used at the discretion of the treating clinician.
Venography
Retrograde spermatic venography is generally considered to be the most sensitive test for the detection of varicoceles. However, it is fairly invasive and usually only performed in conjunction with therapeutic occlusion. Access is usually obtained via the right femoral vein or right internal jugular vein, as described by Seldinger, and a catheter is advanced to the testicular vein and a contrast agent injected. In patients with palpable varicoceles, reflux has been reported in 100% of patients. However, the specificity of this modality has been questioned, as there is a considerable false-positive rate. Netto Júnior and colleagues demonstrated no statistically significant differences in the presence of spermatic vein reflux in subfertile patients with varicoceles, fertile patients with varicoceles, and normal controls.
There is also considerable technical variability with diagnosis, and thus venography is considered an adjunct to physical examination and usually reserved for situations where treatment can be pursued in the same setting. An interesting concept proposed by Hart and colleagues advocates intraoperative spermatic venography during varicocelectomy, with a reported 16% collateral drainage rate that could have resulted in varicocele persistence if those specific veins were not ligated. Given the low recurrence rate and advances with microsurgery, intraoperative spermatic venography is not routinely performed; however, it can provide a more precise anatomic definition of venous anatomy in postsurgical patients with varicocele persistence or recurrence. For this reason, a common indication for venography is a recurrent or persistent postsurgical varicocele; thus, difficult venous anatomy can be well delineated and simultaneous treatment offered. Punekar and colleagues reported a success rate of 85% in patients with recurrent varicoceles using stainless steel coil embolization.
Treatment indications
Infertility
As per the American Urological Association Best Practice Policy “Report on Varicocele and Infertility,” varicoceles should be treated when all the following conditions are met:
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Varicocele is palpable on physical examination of the scrotum.
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The couple has known infertility.
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The female partner has normal fertility or a potentially treatable cause of infertility.
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The male partner has abnormal semen parameters or abnormal results from sperm function tests.
With regards to infertility, varicocele treatment is not indicated if semen parameters are normal or if the varicocele is subclinical. Adult men who are not actively trying to conceive but present with an incidental varicocele should be counseled on fertility risk and offered at least 1 semen analysis to evaluate their reproductive capacity. Although not all men with varicoceles have abnormal semen parameters, a substantial proportion of them may have reduced counts, decreased motility, and/or abnormal morphology. Because they may try to achieve conception sometime in the future, men with clinically palpable varicoceles and abnormal semen parameters should be informed of definitive varicocele treatment options.
Men with clinically palpable varicoceles and normal semen parameters may be at risk for future testicular dysfunction. Witt and Lipshultz demonstrated that varicoceles are capable of causing progressive fertility loss. In their date-matched retrospective analysis, they noted that varicoceles were identified as the cause of infertility in 69% of men with secondary infertility compared with 50% of men with primary infertility, suggesting that varicoceles are progressive lesions resulting in the loss of previously established fertility. Gorelick and Goldstein’s work, as previously discussed, supported this finding. For this reason, young adult men with clinically palpable varicoceles, normal semen parameters, and a desire for future paternity should be offered monitoring with serial semen analyses every 1 to 2 years. If abnormal results are obtained, semen analyses should be repeated, and if progressive dysfunction persists, they can be offered definitive treatment of varicocele. In addition, men with secondary infertility and clinically palpable varicoceles should be offered the same treatment as individuals presenting with primary infertility.
Young men with clinically palpable varicoceles and objective evidence of testicular atrophy may also be considered for varicocele treatment. Semen analyses can be offered to further clarify reproductive potential in this population, although reduced ipsilateral testicular size may alone indicate testicular dysfunction secondary to varicocele. Sigman and Jarow reported that patients with unilateral left varicoceles and ipsilateral testicular hypotrophy had significantly reduced semen parameters compared with patients without hypotrophy. Thus, adolescents and young men with varicocele-associated testicular growth retardation should be offered treatment. In patients with varicoceles but with normal (ipsilateral) testicular size, routine follow-up should include objective measurements of testicular size and/or semen analyses to detect the earliest sign of testicular dysfunction.
With the advent of advanced assisted reproductive technologies (ARTs), many couples with male-factor infertility secondary to varicocele may ultimately choose between varicocele treatment and IUI or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Although many factors may influence this decision, couples should be routinely counseled that varicocele repair might offer a permanent solution to male-factor infertility, whereas IUI or IVF/ICSI must be used for each pregnancy attempt. Moreover, there is considerably greater cost savings for varicocele treatment versus IUI/IVF or IVF in patients with isolated varicocele-related infertility.
Varicocele treatment is not routinely recommended when IVF is necessary secondary to a female factor. However, in certain cases with both male and female factor components, varicocelectomy can augment ART efforts. In some azoospermic or cryptozoospermic patients, varicocele repair can lead to improved numbers of ejaculated sperm, thereby sparing these men a testicular sperm extraction. Kim and colleagues reported that approximately 43% of patients with azoospermia had return of sperm in the ejaculate after unilateral or bilateral varicocelectomy. These patients also underwent simultaneous testicular biopsy, which revealed that only men with severe hypospermatogenesis and maturation arrest spermatid stage had improvement in sperm density (patients with Sertoli-cell-only or maturation arrest spermatocyte stage did not demonstrate a benefit). Although all couples eventually required some form of ART to achieve a pregnancy, this study contends that certain patients with spermatogenic failure and varicoceles may be candidates for varicocele repair, instead of resorting to testicular sperm extraction in preparation for ICSI. Additional studies regarding the benefit of varicocelectomy with ART are discussed a subsequent section.
Hypogonadism
The progressive negative effect of varicoceles on Leydig cell function has been previously discussed along with the association of varicoceles and low serum testosterone in some men. With greater public awareness of hypogonadism and concern for varicoceles as a significant risk factor for androgen deficiency, there is an ongoing debate regarding the benefit of varicocelectomy for improving serum testosterone. Earlier studies did not show a statistically significant increase in serum testosterone after varicocelectomy; however, many of these studies were smaller scale and included patients with normal to above-normal baseline testosterone levels. Meanwhile, studies by Su and colleagues and Tanrikut and colleagues have shown not only that varicocelectomy leads to an improvement in serum testosterone but also that men with lower preoperative testosterone levels derived the most benefit. Hsiao and colleagues corroborated this finding in infertile men with baseline lower testosterone values and confirmed that significant increases in serum testosterone postvaricocelectomy are independent of varicocele grade or age.
Although this biochemical response in previously hypogonadal men is interesting, it is worthwhile to also assess the effects of varicocele treatment on the signs and symptoms of hypogonadism. Many younger men with hypogonadism may present with low energy, diminished libido, and erectile dysfunction (ED). Srini and Veerachari evaluated 200 heterosexual, hypogonadal infertile men with clinical varicoceles and divided them into 2 groups: those who underwent varicocelectomy and those who underwent ART. In the varicocelectomy group, they observed a statistically significant increase in serum testosterone levels with 78% of patients becoming eugonadal. As expected, there was no change in serum testosterone levels in the hypogonadal men with varicoceles who underwent ART. However, they observed a reduction in ED among patients in the varicocelectomy group; the prevalence of ED decreased from 44% to 31%. Meanwhile, there was a mild increase from 39% to 41% in ED among those who were in the ART group and did not have correction of their serum testosterone. Zohdy and colleagues performed a similar study with 141 heterosexual infertile hypogonadal men with clinical varicoceles divided into a varicocelectomy treatment arm and an ART arm. They also reported a significant increase in serum testosterone levels in the varicocelectomy arm with normalization of testosterone levels in 75.5% of these men. Moreover, they reported a significant increase in the International Index of Erectile Function 5 questionnaire results in hypogonadal men undergoing varicocelectomy, suggesting clinical improvement with regards to erectile function in symptomatic men.
Varicocelectomy for men with low testosterone levels is a controversial and an evolving concept; it is not at this time considered to be a standard of care. To date, the body of evidence regarding varicocele treatment and low testosterone has primarily focused on populations of infertile men. Furthermore, there are no studies on the long-term maintenance of higher testosterone levels after varicocele repair. Nonetheless, there is emerging evidence to suggest that microsurgical varicocelectomy may be a promising alternative to the medical treatment of hypogonadism and potentially prevent future androgen deficiency in some men.
Symptomatic Varicoceles
Varicoceles can also present with pain, which is typically a dull ache and localized to the scrotum or inguinal area. There is tremendous variability in the frequency, character, and intensity of this discomfort, and other potential causes of pain must be explored before the varicocele is treated. Common conservative measures include scrotal support/elevation, antiinflammatory medications, and analgesic agents. Patients may also benefit from a referral for pelvic floor physical therapy or consultation with a pain medicine specialist.
When conservative measures prove inadequate, definitive treatment of the varicocele can be offered, although patients should be counseled that surgery may not relieve their discomfort. There is considerable variability regarding surgical outcomes for symptomatic varicoceles, but most reports show a high rate of success in relieving discomfort. These studies include subjects ranging from 11 to 284 patients, although the majority includes data on less than 100 patients. Rates for resolution of pain and improvement of pain after varicocelectomy range from 53% to 94% and 42% to 100%, respectively. Most contemporary studies use the microsurgical subinguinal approach, although all other options such as laparoscopic and robotic techniques have also been used with respectable results.
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